Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi's Sarcoma

Step 1: Inclusion Criteria

1. HIV-1 infection.
2. Biopsy diagnostic of KS at any time prior to study entry.

3. Current limited stage KS using the ACTG criteria documented in the study protocol. The following presentations of stage T1 KS are also eligible at the discretion of the site investigator:

   • Tumor-associated edema limited to the area(s) of KS without significant functional impairment.
   • Oral KS that consists of flat (non-nodular and non-ulcerating) lesions confined to the soft palate, hard palate, gums, and buccal mucosa.
   • Asymptomatic gastrointestinal KS (i.e., no unexplained abdominal pain or gastrointestinal bleeding).
4. A minimum of 5 cutaneous marker lesions
5. Certain laboratory values obtained within 14 days prior to study entry.
6. Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 7 days prior to study entry.
7. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).

8. Female participants who are participating in sexual activity that could lead to pregnancy must agree to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, and/or hormonal-based contraception.

   For Etoposide, confirmation of lack of reproductive potential is required for all participants. More information on this criterion can be found in the study protocol.

9. Ability to swallow oral medications.
10. Karnofsky performance score >= 60 within 30 days prior to entry.
11. Ability and willingness of participant or legal guardian/representative to provide informed consent.
12. Peripheral blood CD4+ lymphocyte cell count obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
13. For treatment-experienced patients, the availability of an ART regimen that includes at least two ART drugs that in the opinion of the site investigator are expected to have activity based on historical genotypic testing (if available) and treatment history.
14. For participants who are to receive ART other than EFV/TDF/FTC, the availability of those ART components.

Step 2: Inclusion Criteria

1. KS progression as defined in the study protocol or KS progression after a complete or partial response as defined in the study protocol, while on Step 1 Arm 1A, between weeks 8 and 80.
2. Need for ET for treatment of KS progression, in the opinion of the site investigator, after confirmation of KS progression by the IERC.
3. Willingness to receive ET for treatment of KS progression.
4. Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 7 days prior to initiating ET.
5. Karnofsky Performance Score >= 50.
6. Certain laboratory values obtained within 14 days prior to Step 2 entry.
7. Ability to swallow oral medications.
8. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
9. Female participants who are participating in sexual activity that could lead to pregnancy must agree to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, hormonal-based contraception.

For Etoposide, confirmation of lack of reproductive potential is required for all participants. More information on this criterion can be found in the study protocol.

Step 3: Inclusion Criteria

1. Received at least one dose of ET (Arm 1B or Arm 2A)

Step 1: Exclusion Criteria

1. Any manifestation of KS which, in the opinion of the site investigator, requires immediate chemotherapy.
2. Receipt of ART within 6 months prior to study entry.
3. Biopsy proven KS during previous ART.
4. Breastfeeding.
5. Allergy/sensitivity to any study drug or its formulations.
6. Any prior systemic anti-neoplastic treatment for KS (including chemotherapy, biological therapy, immunotherapy or investigational therapy).
7. Any prior local treatment of cutaneous marker lesions unless there was evidence of a clear-cut progression of the lesion.
8. Receipt of any investigational therapy within 30 days prior to study entry.
9. Current or anticipated receipt of any of the prohibited medications indicated in the PSWP.
10. In the opinion of the site investigator, any psychological or social condition, or addictive disorder that would preclude compliance with the protocol.
11. Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to study entry and/or is not clinically stable.

Step 2: Exclusion Criteria

1. Current chronic, acute, or recurrent infections that are serious, in the opinion of the site investigator, for which the participant has not completed at least 14 days of therapy prior to initiating ET and/or is not clinically stable.
2. Current or anticipated receipt of any of the prohibited medications indicated in the PSWP.
3. Breastfeeding.

There are no exclusion criteria for Step 3.